siRNA Delivery Using a Cationic-Lipid-Based Highly Selective Human DNA Ligase I Inhibitor

The present article illustrates the serendipitous discovery of a cationic-lipid-based human DNA ligase (hLig) I inhibitor and the development of siRNA delivering, a hLigI-targeted cationic-lipid-based nonviral vector. We have tested a small in-house library of structurally similar cationic lipo-anis...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2018-01, Vol.10 (2), p.1616-1622
Main Authors: Bathula, Surendar R, Sharma, Komal, Singh, Deependra K, Reddy, Muktapuram P, Sajja, Pushpa R, Deshmukh, Amit L, Banerjee, Dibyendu
Format: Article
Language:English
Subjects:
Cations
DNA Ligase ATP - metabolism
DNA-Binding Proteins
Humans
Lipids
Liposomes
RNA, Small Interfering
Transfection
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Summary:The present article illustrates the serendipitous discovery of a cationic-lipid-based human DNA ligase (hLig) I inhibitor and the development of siRNA delivering, a hLigI-targeted cationic-lipid-based nonviral vector. We have tested a small in-house library of structurally similar cationic lipo-anisamides for antiligase activity, and amongst tested, N-dodecyl-N-(2-(4-methoxybenzamido)­ethyl)-N-methyldodecan-1-ammonium iodide (C12M) selectively and efficiently inhibited the enzyme activity of hLigI, compared to other human ligases (hLigIIIβ and hLigIV/XRCC4) and bacterial T4 DNA ligase. Furthermore, upon hydration with equimolar cholesterol, C12M produced antiligase cationic liposomes, which transfected survivin siRNA and showed significant inhibition of tumor growth.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.7b19193